Compositions that metabolize or sequester free sugar monomers and uses thereof

Abstract

Compositions comprising at least two non-pathogenic microbes are described herein. The non-pathogenic microbes may be from a first species capable of internalizing and/or metabolizing dietary glycans and/or from a second species capable of consuming and metabolizing free sugar monomers. Methods of making and use in treating and/or preventing the overgrowth of pathogenic bacteria in mammals are also described herein.

1 .- 60 . (canceled) 
     
     
         61 . A composition comprising at least two non-pathogenic microbes, wherein one of the at least two non-pathogenic microbes is from a first species capable of internalizing and/or metabolizing dietary glycans, and wherein one of the at least two non-pathogenic microbes is from a second species capable of consuming and metabolizing free sugar monomers. 
     
     
         62 . The composition of  claim 61 , wherein the composition is capable of growing on dietary glycans,
 wherein the dietary glycans comprises sialic acid and/or fucose, and from 1-10% of sialic acid and/or from 1-10% of the fucose, or from less than 1% of sialic acid and less than 1% of the fucose remains as free sugar monomers after a culture of the composition has ceased to grow; and   wherein at least one of the non-pathogenic microbes comprises comprises a gene coding for
 a sialidase or a fucosidase, which may be in the first species of the non-pathogenic microbe; or 
 a sialic acid or a fucose transporter, which may be in the first species of the non-pathogenic microbe; or 
 a complex oligosaccharide transporter. 
   
     
     
         63 . The composition of  claim 61 , wherein the first species of non-pathogenic microbe is selected from the group consisting of
 a member of the genus  Bifidobacterium;      a member of the genus  Bifidobacterium , wherein the  Bifidobacterium  is  B. longum, B. breve , or  B. pseudocatenulaturn;      a member of the genus  Bifidobacterium , wherein the  Bifidobacterium  is  B. longum  subsp.  infantis ; and     B. longum  subsp.  infantis , wherein the  B. longum  subsp.  infantis  is activated.   
     
     
         64 . The composition of  claim 61 ,
 wherein the free sugar monomers include fucose, sialic acid, N-acetylglucosamine, N-acetylgalactosamine, gluconate, glucose, galactose, glucosinate, lactose, sialyllactose, fucosyllactose, lacto-N-biose, and mixtures thereof; or   wherein the second species is selected based on the free sugar monomers that are present or predicted to be present in an infant mammal; or   wherein the second species is selected based on the free sugar monomers that are present in an infant mammal, the presence being determined by measuring the free sugar monomers in a fecal sample of the infant mammal; or   wherein the second species is selected based on the free sugar monomers that are present in an infant mammal, the presence being determined by measuring the free sugar monomers in a fecal sample of the infant mammal in an amount of at least 5 μg of free sugar monomer per gram of dry weight of feces; or   wherein the free sugar monomers are predicted to be present in an infant mammal, and wherein the presence is predicted based on a pathogenic bloom of the infant mammal; or   wherein the free sugar monomers are predicted to be present in an infant mammal based on a pathogenic bloom of the infant mammal, the pathogen of the pathogenic bloom optionally being a member of the Class  Clostridium  or Phylum Proteobacteria; or   wherein the free sugar monomers are predicted to be present in an infant mammal based on a pathogenic bloom of the infant mammal, the pathogen of the pathogenic bloom optionally being  C. difficile  or  C. perfringens ; or   wherein the second species is selected based on the free sugar monomers that are preferred by a pathogen, optionally wherein there is an increased likelihood of a pathogenic overpopulation of the pathogen in an infant mammal; or   wherein the second species is selected based on the free sugar monomers that are preferred by a pathogen, optionally wherein there is an increased likelihood of a pathogenic overpopulation of the pathogen in an infant mammal due to an outbreak in the surroundings of the infant mammal; or   wherein the second species is selected based on the free sugar monomers that are preferred by a pathogen, wherein there is an increased likelihood of a pathogenic overpopulation of the pathogen in an infant mammal, and wherein the pathogen is a member of the Class Clostridia or Phylum Proteobacteria; or   wherein the second species is selected based on the free sugar monomers that are preferred by a pathogen, wherein there is an increased likelihood of a pathogenic overpopulation of the pathogen in an infant mammal, and wherein the pathogen is  C. difficile  or  C. perfringens.      
     
     
         65 . The composition of  claim 61 , wherein the second species of non-pathogenic microbe is
 a member of the genus  Bifidobacterium, Lactobacillus , and/or  Pediococcus ; or     B. infantis, B. breve, B. bifidum, B. longum, B. adolescentis, B. animalis , or  B. pseudocatenulatum ; or     L. planatarum, L. casei, L. rhamnosus, L. brevis, L. fermenturn, L. crispatus, L. johnsonii, L. gasseri, L. mucosae , or  L. salivarius ; or     P. acidilacti, P. entosaceus, P. stilesii, P. argentinicus , or  P. claussenii.      
     
     
         66 . The composition of  claim 61 , wherein
 the non-pathogenic microbes are present in an amount of 10 million to 500 billion cfu per gram; or   the first species of non-pathogenic microbe is present in an amount of about 10% to about 90% of total amount of the non-pathogenic microbes; or   the first species of non-pathogenic microbe is present in an amount of about 20% to about 80% of total amount of the non-pathogenic microbes; or   the second species of non-pathogenic microbe is present in an amount of about 10% to about 90% of total amount of non-pathogenic microbes; or   the second species of non-pathogenic microbe is present in an amount of about 20% to about 80% of total amount of non-pathogenic microbes; or   the first species is present in an amount of between 10 4  cfu and 10 12  cfu per gram dry weight; or   the second species is present in an amount of between 10 4  cfu and 10 12  cfu per gram dry weight.   
     
     
         67 . The composition of  claim 61 , wherein
 the composition is in the form of a dry powder or a dry powder suspended in an oil; or   the composition is spray dried or freeze-dried; or   the composition is freeze-dried in the presence of a suitable cryoprotectant;   and if the composition is freeze-dried in the presence of a suitable cryoprotectant, optionally the suitable cryoprotectant is glucose, lactose, raffinose, sucrose, trehalose, adonitol, glycerol, mannitol, methanol, polyethylene glycol, propylene glycol, ribitol, alginate, bovine serum albumin, carnitine, citrate, cysteine, dextran, dimethyl sulphoxide, sodium glutamate, glycine betaine, glycogen, hypotaurine, peptone, polyvinyl pyrrolidone, or taurine.   
     
     
         68 . The composition of  claim 61 , further comprising
 about 5 to 90% by weight dietary glycans: or   about 5 to 90% by weight dietary glycans derived from a human, swine, or bovine source.   
     
     
         69 . A method of improving the health of or treating dysbiosis in a subject, the method comprising
 administering to subject, the composition of  claim 61 ; or   administering, based on the presence of said free sugar monomers in the subject's feces, a composition comprising non-pathogenic microbes, wherein the non-pathogenic microbes are capable of metabolizing and/or sequestering the free sugar monomers; or   administering, based on the presence of said free sugar monomers in the subject's feces, a composition comprising non-pathogenic microbes, the non-pathogenic microbes being capable of metabolizing and/or sequestering the free sugar monomers, the composition further comprising a non-pathogenic microbe capable of internalizing and/or metabolizing dietary glycans.   
     
     
         70 . A method of improving the health or treating dysbiosis in an infant mammal, the method comprising administering to the infant mammal the composition of  claim 61 , wherein the infant mammal is receiving dietary glycans contemporaneously with the administration of the composition or the infant mammal is a nursing infant mammal. 
     
     
         71 . The method of  claim 69 , wherein the subject is a mammal; optionally a mammal that is a human, a cow, a pig, a rabbit, a goat, a sheep, a cat, a dog, a horse, or a camel; or a mammal that is an infant. 
     
     
         72 . The method of  claim 69 , wherein the subject is an infant mammal to whom the composition of  claim 61  has been administered,
 wherein the free sugar monomers consumed by the second species are those present as a consequence of prior antibiotic administration; or 
 wherein the composition is first administered at a period of within 96 hours of the birth of the infant mammal. 
 
     
     
         73 . A method of detecting a dysbiotic subject, comprising determining a presence of free sugar monomers in the subject's feces and reporting the presence of free sugar monomers.